• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.775-780
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• 2014

Objectives: TCR-gamma-delta+T cells (${\gamma}{\delta}$ T cells) are non-conventional T lymphocytes that can recognize and eradicate tumor cells. Our previous studies showed that infiltration and function of ${\gamma}{\delta}$ T cells were substantially attenuated in hepatocellular carcinoma (HCC). However, their prognostic value was not clarified. Methods: The association between ${\gamma}{\delta}$ T cells and the clinical outcomes was determined by immunohistochemistry (IHC) in a HCC patient cohort (n = 342). Results:Immunohistochemistry showed decreased infiltration of ${\gamma}{\delta}$ T cells in tumoral tissues compared with paired peritumoral tissues. The counts of ${\gamma}{\delta}$ T cells in peritumoral tissues were negatively correlated with tumor size (P = 0.005). Survival analysis showed that the levels of peritumoral ${\gamma}{\delta}$T cells were related to both time to recurrence (TTR) and overall survival (OS) (P = 0.010 and P = 0.036, respectively) in univariate analysis, and related to TTR in multivariate analysis (P = 0.014, H.R. [95% CI] = 0.682 [0.502-0.927]). Furthermore, the level of peritumoral ${\gamma}{\delta}$ T cells showed independent prognostic value for TTR in Barcelona Clinic Liver Cancer (BCLC) stage A patients (P = 0.038, H.R. [95% CI] = 0.727 [0.537-0.984]). However, tumoral ${\gamma}{\delta}$ T cells did not show independent prognostic value for either TTR or OS in HCC patients. Conclusions: Low counts of ${\gamma}{\delta}$ T cells in peritumoral liver tissue are related to a higher incidence of recurrence in HCC and can predict postoperative recurrence, especially in those with early-stage HCC.

• Genomics & Informatics
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• v.1 no.2
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• pp.101-107
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• 2003

Loss of heterozygosity (LOH) has been used to detect deleted regions of a specific chromosome in cancer cells. LOH on chromosome 16q has been reported to occur frequently in progressed hepatocellular carcinoma (HCC). Liver tissues from 37 Korean HCC patients were analyzed for LOH by using 25 polymorphic microsatellite markers distributed along 16q. Out of the 37 HCC patients studied, 21 patients (56.8%) showed LOH in various regions of 16q with at least one polymorphic marker. Puring the analysis of these 21 LOH cases, 6 patients showed interstitial LOHs in which the boundary of the LOH region was defined. With two rounds of LOH analysis, five commonly occurring interstitial LOH regions were identified; 16q21-22.1, 16q22.2 - 22.3, 16q22.3, 16q23.2 and 16q23.3 - 24.1. Among the five LOH regions the 16q23.3 - 24.1 region has been reported to be related with chromosome instability. A complete physical map, which covers the 3.2 Mb region of 16q23.3 - 24.1 (D16S402 and D16S486), was constructed to identify novel candidate tumor suppressor genes. We provide the minimally tiling path map consisting of 28 BAC clones. There was one gap between NT_10422.11 and NT_019609.9 of the human genome sequence contig (NCBI sequence build 33, April 29, 2003). This gap can be filled by sequencing the R-1425M20 clone which bridges these sequence contigs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.225-229
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• 2012

Background: Males have a higher prevalence of hepatocellular carcinoma (HCC) than females in general, but the reasons for the sex disparity are still obscure. DNA copy number alteration (CNA) is a major feature of solid tumors including HCC, but whether CNA plays a role in sex-related differences in HCC development has never been evaluated. Methods: High-resolution array comparative genomic hybridization (CGH) was used to examine 17 female and 46 male HCC patients with chronic hepatitis B virus (HBV) infection in Shanghai, China. Two-tailed Fisher's exact or ${\chi}^2$ tests was used to compare CNAs between females and males. Results: The overall frequencies and patterns of CNAs in female and male cases were similar. However, female HCC tumors presented more copy number gains compared to those in males on 1q21.3-q22 (76.5% vs. 37.0%, P = 0.009), 11q11 (35.3% vs. 0.0%, P = 0.0002) and 19q13.31-q13.32 (23.5% vs. 0.0%, P = 0.004), and loss on 16p11.2 (35.3% vs. 6.5%, P = 0.009). Relative to females, male cases had greater copy number loss on 11q11 (63.0% vs. 17.6%, P = 0.002). Further analyses showed that 11q11 gain correlated with 19q13.31-q13.32 gain (P = 0.042), 11q11 loss (P = 0.011) and 16p11.2 loss (P = 0.033), while 1q21.3-q22 gain correlated with 19q13.31-q13.32 gain (P = 0.046). Conclusions: These findings suggest that CNAs may play a role in sex-related differences in HBVassociated HCC development.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.219-224
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• 2016

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver making up more than 80 percent of cases. It is known to be the sixth most prevalent cancer and the third most frequent cause of cancer related death worldwide. Epigenetic regulation constitutes an important mechanism by which dietary components can selectively activate or inactivate target gene expression. The miR-34 family members including mir-34a, mir-34b and mir-34c are tumor suppressor micro RNAs, which are expressed in the majority of normal tissues. Several studies have indicated silencing of miR-34 expression via DNA methylation in multiple types of cancers. Bioactive nutrients like curcumin (Cur) have excellent anticarcinogenic activity and minimal toxic manifestations in biological systems. This compound has recently been determined to induce epigenetic changes. However, Cur is lipophilic and has a poor systemic bioavailability and poor absorption. Its bioavailability is increased through employing dendrosome nanoparticles. The aim of the current study was to investigate the effect of dendrosomal nanocurcumin (DNC) on expression of mir-34 family members in two HCC cell lines, HepG2 and Huh7. We performed the MTT assay to evaluate DNC and dendrosome effects on cell viability. The ability of DNC to alter expression of the mir-34 family and DNA methyltransferases (DNMT1, DNMT3A and 3B) was evaluated using semi-quantitative and quantitative PCR. We observed the entrance of DNC into HepG2 and Huh7 cells. Gene expression assays indicated that DNC treatment upregulated mir34a, mir34b and mir34c expression (P<0.05) as well as downregulated DNMT1, DNMT3A and DNMT3B expression (P<0.05) in both HepG2 and Huh7 cell lines. DNC also reduced viability of Huh7 and HepG2 cells through restoration of miR-34s expression. We showed that DNC could awaken the epigenetically silenced miR-34 family by downregulation of DNMTs. Our findings suggest that DNC has potential in epigenetic therapy of HCC.

• Health Policy and Management
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• v.27 no.2
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• pp.149-156
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• 2017

Background: This study was conducted to evaluate the performance of the Hierarchical Condition Category (HCC) model, identify potentially high-cost patients, and examine the effects of adding prior utilization to the risk model using Korean claims data. Methods: We incorporated 2 years of data from the National Health Insurance Services-National Sample Cohort. Five risk models were used to predict health expenditures: model 1 (age/sex groups), model 2 (the Center for Medicare and Medicaid Services-HCC with age/sex groups), model 3 (selected 54 HCCs with age/sex groups), model 4 (bed-days of care plus model 3), and model 5 (medication-days plus model 3). We evaluated model performance using $R^2$ at individual level, predictive positive value (PPV) of the top 5% of high-cost patients, and predictive ratio (PR) within subgroups. Results: The suitability of the model, including prior use, bed-days, and medication-days, was better than other models. $R^2$ values were 8%, 39%, 37%, 43%, and 57% with model 1, 2, 3, 4, and 5, respectively. After being removed the extreme values, the corresponding $R^2$ values were slightly improved in all models. PPVs were 16.4%, 25.2%, 25.1%, 33.8%, and 53.8%. Total expenditure was underpredicted for the highest expenditure group and overpredicted for the four other groups. PR had a tendency to decrease from younger group to older group in both female and male. Conclusion: The risk adjustment models are important in plan payment, reimbursement, profiling, and research. Combined prior use and diagnostic data are more powerful to predict health costs and to identify high-cost patients.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2003.10a
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• pp.107-107
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• 2003

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.457-468
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• 2022

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4037-4041
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• 2016

Background: Hepatocellular carcinoma (HCC) is a common cancer that is frequently diagnosed at an advanced stage. Transarterial chemoembolisation (TACE) is an effective palliative treatment for patients who are not eligible for curative treatment. The two main methods for performing TACE are conventional (c-TACE) or with drug eluting beads (DEB-TACE). We sought to compare survival rates and tumour response between patients undergoing c-TACE and DEB-TACE at our centre. Materials and Methods: A retrospective cohort study of patients undergoing either treatment was carried out from January 2009 to December 2014. Tumour response to the procedures was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Kaplan-Meier analysis was used to assess and compare the overall survival in the two groups. Results: A total of 79 patients were analysed (34 had c-TACE, 45 had DEB-TACE) with a median follow-up of 11.8 months. A total of 20 patients in the c-TACE group (80%) and 12 patients in the DEB-TACE group (44%) died during the follow up period. The median survival durations in the c-TACE and DEB-TACE groups were $4.9{\pm}3.2$ months and $8.3{\pm}2.0$ months respectively (p=0.008). There was no statistically significant difference noted among the two groups with respect to mRECIST criteria. Conclusions: DEB-TACE demonstrated a significant improvement in overall survival rates for patients with unresectable HCC when compared to c-TACE. It is a safe and promising approach and should potentially be considered as a standard of care in the management of unresectable HCC.

• Journal of Electrical Engineering and Technology
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• v.13 no.1
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• pp.270-279
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• 2018

This paper elucidates a hysteresis current controller for enhancing the performance of static synchronous compensator (STATCOM) using cascaded H-bridge multilevel inverter. Due to the rising power demand and growing conventional generation costs a new alternative in renewable energy source is gaining popularity and recognition. A five level single phase cascaded multilevel inverter with two separated dc sources, which is energized by photovoltaic - wind hybrid energy source. The voltages across the each dc source is balanced and standardized by the proposed hysteresis current controller. The performance of STATCOM is analyzed by connecting with grid connected system, under the steady state & dynamic state. To reduce the Total Harmonic Distortion (THD) and to improve the output voltage, closed loop hysteresis current control is achieved using PLL and PI controller. The performance of the proposed system is scrutinized through various simulation results using matlab/simulink and hardware results are also verified with simulation results.

• Journal of The Korean Astronomical Society
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• v.31 no.2
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• pp.117-125
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• 1998

We have observed the 10-9 transitions of $HC_3N$ and its $^{13}C$ substitutes ($H^{13}CCCN,\;HC^{13}CCN$, and $HCC^{13}CN$), and the vibration ally excited 12-11 ($v_r=1$) $HC_3N$ transition toward the Sgr B2 molecular cloud. The observed $HC_3N$ emission shows an elongated shape around the Principal Cloud ($\~$4.5 pc in R.A. $\times$ 7.4 pc in Decl.). The optically thin $H^{13}CCCN$ line peaks around the (N) core and we derive the total column density $N(H^{13}CCCN) = 4 {\times}10^{13} cm^{-2}$ at this position. Toward the 2' N cloud which shows the peculiar chemistry, the $HC_3N$ lines show enhancements compared to the extended envelope. The shocks of the 2' N may have resulted in the enhancement of $HC_3N$. The hot component of $HC_3N$ is strongly concentrated around the (N) core and its HPW is $\~$0.9 pc in diameter. We derive the lower limit of the abundance ratio $N(HC_3N)/N(H^{13}CCCN)$ to be larger than 40 in most regions except the (M) and (N) cores. The fractionation processes of $^{13}C $at this region may not be as effective as previously reported.